Potential mechanisms explaining why hydrolyzed casein‐based diets outclass single amino acid‐based diets in the prevention of autoimmune diabetes in diabetes‐prone BB rats

Visser, J.H.M.; Bos, Nicolaas A.; Harthoorn, Lucien F.; Stellaard, Frans; Beijer-Liefers, Suzanne; Rozing, Jan; Tol, Eric A.F. van

doi:10.1002/dmrr.2311

Cited by 36 publications

(28 citation statements)

References 41 publications

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“…HC intervention is associated with changes in the gut microbiota including increased Lactobacilli and decreased Bacteroide s spp. levels (28). To test whether dietary changes would similarly affect sialitis to the same degree as it affects diabetes (29), we compared disease development in mice fed regular chow and HC diet.…”

Section: Resultsmentioning

confidence: 99%

Cutting Edge: Commensal Microbiota Has Disparate Effects on Manifestations of Polyglandular Autoimmune Inflammation

Hansen

Yurkovetskiy

Chervonsky

2016

The Journal of Immunology

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Polyglandular autoimmune inflammation accompanies Type 1 diabetes (T1D) in NOD mice affecting organs like thyroid and salivary glands. Whereas commensals are not required for T1D progression, germ-free (GF) mice had a very low degree of sialitis, which was restored by colonization with select microbial lineages. Moreover, unlike T1D, which is blocked in mice lacking MyD88-signaling adaptor under conventional but not under GF housing conditions, sialitis did not develop in MyD88-negative GF mice. Thus, microbes and MyD88-dependent signaling are critically required for sialitis development. The severity of sialitis did not correlate with the degree of insulitis in the same animal, was less sensitive to T1D-reducing diet, but was similar to T1D in microbiota-dependent sexual dimorphism. The unexpected distinction in requirements for the microbiota for different autoimmune pathologies within the same organism is crucial for understanding the nature of microbial involvement in complex autoimmune disorders including human autoimmune polyglandular syndromes.

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Section: Resultsmentioning

confidence: 99%

Cutting Edge: Commensal Microbiota Has Disparate Effects on Manifestations of Polyglandular Autoimmune Inflammation

Hansen

Yurkovetskiy

Chervonsky

2016

The Journal of Immunology

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“…This suggests that HC feeding did not afford protection from T1D in SPF rats by shifting the bacterial profile toward the control strain profile. Nonetheless, the microbiota are different in BBdp rats that develop diabetes (31–33), and administering protective bacteria can prevent T1D (34). When BBdp Wor/Gro rats were treated with antibiotics and fed an HC diet from weaning, T1D was completely prevented (31), in agreement with the present results (Fig.…”

Section: Discussionmentioning

confidence: 99%

Promotion of Autoimmune Diabetes by Cereal Diet in the Presence or Absence of Microbes Associated With Gut Immune Activation, Regulatory Imbalance, and Altered Cathelicidin Antimicrobial Peptide

et al. 2013

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We are exposed to millions of microbial and dietary antigens via the gastrointestinal tract, which likely play a key role in type 1 diabetes (T1D). We differentiated the effects of these two major environmental factors on gut immunity and T1D. Diabetes-prone BioBreeding (BBdp) rats were housed in specific pathogen-free (SPF) or germ-free (GF) conditions and weaned onto diabetes-promoting cereal diets or a protective low-antigen hydrolyzed casein (HC) diet, and T1D incidence was monitored. Fecal microbiota 16S rRNA genes, immune cell distribution, and gene expression in the jejunum were analyzed. T1D was highest in cereal-SPF (65%) and cereal-GF rats (53%) but inhibited and delayed in HC-fed counterparts. Nearly all HC-GF rats remained diabetes-free, whereas HC-fed SPF rats were less protected (7 vs. 29%). Bacterial communities differed in SPF rats fed cereal compared with HC. Cereal-SPF rats displayed increased gut CD3+ and CD8α+ lymphocytes, ratio of Ifng to Il4 mRNA, and Lck expression, indicating T-cell activation. The ratio of CD3+ T cells expressing the Treg marker Foxp3+ was highest in HC-GF and lowest in cereal-SPF rats. Resident CD163+ M2 macrophages were increased in HC-protected rats. The cathelicidin antimicrobial peptide (Camp) gene was upregulated in the jejunum of HC diet–protected rats, and CAMP+ cells colocalized with CD163. A cereal diet was a stronger promoter of T1D than gut microbes in association with impaired gut immune homeostasis.

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“…Current, although limited, data in human type 1 diabetes cohorts suggests that butyrate-and lactate-producing bacteria are associated with protection from type 1 diabetes-related autoimmunity [7], and that children with type 1 diabetesrelated autoimmunity suffer from an abundance of bacteria of the genus Bacteroides [8]. In addition, a recent study in the diabetes-prone BB model suggests that Lactobacilli were decreased in diabetic animals and restored by CH supplementation [39]. The role of Lactobacilli could thus be different between these two animal models of type 1 diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…The fact that NOD mice fed a CH diet had more intact barrier function is in strong support of this. A recent study in BB rats also indicates that peptides from CH combined with a protein-free diet improve gut barrier function [39]. Contact with microbial factors induces tolerance to toll-like receptor-4 signalling in epithelial cells of the neonatal small intestine, which protects epithelial cells from a deleterious inflammatory response [40].…”

Section: Discussionmentioning

confidence: 99%

Casein hydrolysate diet controls intestinal T cell activation, free radical production and microbial colonisation in NOD mice

Emani¹,

Asghar

Toivonen³

et al. 2013

Diabetologia

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Aims/hypothesis Dietary and microbial factors and the gut immune system are important in autoimmune diabetes. We evaluated inflammatory activity in the whole gut in prediabetic NOD mice using ex vivo imaging of reactive oxygen and nitrogen species (RONS), and correlated this with the above-mentioned factors. Methods NOD mice were fed a normal diet or an antidiabetogenic casein hydrolysate (CH) diet. RONS activity was detected by chemiluminescence imaging of the whole gut. Proinflammatory and T cell cytokines were studied in the gut and islets, and dietary effects on gut microbiota and short-chain fatty acids were determined. Results Prediabetic NOD mice displayed high RONS activity in the epithelial cells of the distal small intestine, in conjunction with a proinflammatory cytokine profile. RONS production was effectively reduced by the CH diet, which also controlled (1) the expression of proinflammatory cytokines and colonisation-dependent RegIIIγ (also known as Reg3g) in ileum; (2) intestinal T cell activation; and (3) islet cytokines. The CH diet diminished microbial colonisation, increased the Bacteroidetes:Firmicutes ratio, and reduced lactic acid and butyric acid production in the gut. Conclusions/interpretation Epithelial RONS production and proinflammatory T cell activation appears in the ileum of NOD mice after weaning to normal laboratory chow, but not after weaning to an anti-diabetogenic CH diet. Our data suggest a link between dietary factors, microbial colonisation and mucosal immune activation in NOD mice.

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Potential mechanisms explaining why hydrolyzed casein‐based diets outclass single amino acid‐based diets in the prevention of autoimmune diabetes in diabetes‐prone BB rats

Abstract: Casein hydrolysates were found superior to AA-mix in autoimmune diabetes prevention. This suggests the presence of specific peptides that beneficially affect mechanisms that may play a critical role in autoimmune diabetes pathogenesis.

Cited by 36 publications

References 41 publications

Cutting Edge: Commensal Microbiota Has Disparate Effects on Manifestations of Polyglandular Autoimmune Inflammation

Cutting Edge: Commensal Microbiota Has Disparate Effects on Manifestations of Polyglandular Autoimmune Inflammation

Promotion of Autoimmune Diabetes by Cereal Diet in the Presence or Absence of Microbes Associated With Gut Immune Activation, Regulatory Imbalance, and Altered Cathelicidin Antimicrobial Peptide

Casein hydrolysate diet controls intestinal T cell activation, free radical production and microbial colonisation in NOD mice

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